Wyeth Petitions FDA on Bioidentical Hormones

The surprising results from the Women's Health Initiative, the largest federally-funded study of women's health conditions, caused many menopausal women to scorn hormone replacement therapy (HRT) and look for other ways to manage their symptoms.

One outcome was an increase in demand for "natural" hormones -- despite questionable scientific evidence that these so-called bioidentical compounds have a better safety profile than their synthetic counterparts.

Now Wyeth -- which makes HRT products Premarin, Premphase, and Prempro -- is petitioning FDA to provide more oversight of bioidentical hormones and crack down on pharmacies that are mass marketing these specialty formulas.

With a doctor's prescription, pharmacists can customize drugs for patients who can't take the standard treatment -- and some have substituted plant-based hormones for the synthetic ones used by Wyeth.

Susan Bishop, director of federal regulatory affairs at the American Pharmaceutical Association, noted that since the practice of pharmacy is regulated by the states, FDA has limited power to regulate compounding.

"We're concerned with Wyeth's petition because it is asking FDA to do something that's not under its authority," she said.

FDA can, however, regulate products that are manufactured in large quantities. But Bishop noted, "It's very difficult to draw a fine line between compounding and manufacturing. That's something FDA has struggled with for a long time."

Wyeth insists that it is not going after the legal practice of compounding, but opposes the mass marketing of bioidentical products as "safer" alternatives to its HRT drugs.

"We need to raise the level of noise," said Ginger Constantine, MD, vice president of women's healthcare and bone repair at Wyeth. "If a woman doesn't know what she's taking, she's potentially at risk."

Wyeth is requesting that FDA enforce provisions of the Food, Drug, and Cosmetic Act (FDCA) that require risk information on labels, package insets, and in advertisements. It is also asking the regulatory agency to issue an FDA Alert or Talk Paper to warn patients and physicians that bioidentical hormones could very well carry the same risks as synthetic estrogens.

"The absence of a warning makes people think it's risk-free," Constantine said.

Michelle Warren, MD, a professor of medicine and obstetrics and gynecology at Columbia University Medical Center, noted there has been a "tremendous" increase in demand for bioidentical HRT -- especially after Suzanne Somers promoted it in a recent book.

As a result of the Women's Health Initiative findings, "there was a lot of fear in the menopausal area," Warren said. "Very often pseudo-science comes to fill the void. The patient has to know that the risks are the same."

Groups such as the International Academy of Compounding Pharmacists (IACP) oppose the company's petition.

Jeffrey Gibbs, an attorney at Hyman, Phelps & McNamara, the firm that represents the IACP, noted that FDA has issued compliance policy guidance on compounding, but never solicited public comment. Therefore, the issue of marketing remains an "open question."

"FDA has been relying on the theory that compounded therapies are new drugs," he said, adding that a federal district court judge in Midland, TX, ruled last month that compounded drugs are not unapproved treatments under the FDCA.

Wyeth's petition lists a number of instances when FDA has sent warning letters to compounding pharmacies. They include: pharmacies that were using active ingredients not approved by FDA, pharmacies that were distributing compounded drugs in large quantities, and pharmacies that were providing samples of compounded drugs to physicians.

But a spokeswoman at FDA confirmed that the agency's purview in this area is uncertain.

"We're still reviewing the comments," she said. "We're going to have to decide which direction to go in."